We operate two clinical centers of Look AHEAD, a multicenter randomized clinical trial of weight loss for prevention of complications of type 2 diabetes. Since the clinical trial began in 2002, 5,145 volunteers with type 2 diabetes who were 45-76 years of age and overweight or obese (body mass index > 25 kg/m2) were enrolled in either the intensive lifestyle intervention (ILI) program or the diabetes support and education (DSE) program. The Diabetes Epidemiology and Clinical Research Section clinics enrolled 244 of these participants. The study has reported success in achieving and maintaining weight loss in the ILI group, while there was little weight loss on average in the DSE group. During the first four years after enrollment, the average weight losses were 6.2% in the ILI group and 0.9% in the DSE group. Effects of the weight loss on several health outcomes were reported in previous years. Several more health outcomes were reported during the current fiscal year. Islet autoantibodies in type 2 diabetes. Islet autoantibodies are typically associated with type 1 diabetes, but have been found in patients diagnosed with type 2 diabetes in whom they are associated with lower adiposity. The significance of autoantibody positivity in overweight and obese patients is not well understood. The aim of this study was to determine the prevalence and clinical significance of islet autoantibodies in overweight/obese adults diagnosed with type 2 diabetes. This study includes 204 participants at one site of the multicenter Look AHEAD trial which randomized overweight/obese adults diagnosed with type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. We measured antibodies to glutamic acid decarboxylase, insulinoma antigen-2, and zinc transporter 8. Thirteen participants (6.4%) were autoantibody positive, including six of 47 participants (12.8%) with BMI 40 kg/m2. At baseline, autoantibody positive participants had higher HDL cholesterol and lower fasting C-peptide. Over four years, auto-antibody positive participants lost 5.1 kg more weight than autoantibody negative participants. Longitudinal changes in hemoglobin A1c did not differ by autoantibody status, though autoantibody positive participants were more likely to increase the number of antihyperglycemic medications or initiate insulin. Association of depression with cardiovascular events. Analyses of depression and incident cardiovascular disease (CVD) were performed in the Look AHEAD weight loss trial after a median follow-up of 9.6 years. Depression symptoms were signicantly associated with a composite secondary outcome comprising CVD death, nonfatal myocardial infarction, nonfatal stroke, hospitalized angina, congestive heart failure, peripheral vascular disease, coronary artery bypass graft, and carotid endarterectomy. Signicant sex inter-actions were observed for Beck Depression Inventory (BDI) score. BDI score was signicantly associated with higher probability of this composite outcome in men, but was not associated with the outcome in women. BDI score was positively associated with this composite outcome in men but was negatively associated in women. Sex differences in the association of depression symptoms and ADM use with incident CVD warrant further investigation. Racial-ethnic differences in weight loss in adults with type 2 diabetes. We characterized weight loss, treatment engagement, and weight control strategies used by African American, Hispanic, and non-Hispanic white participants in the Action for Health in Diabetes Intensive Lifestyle Intervention by racial/ethnic and sex subgroups. All subgroups averaged weight losses 5% in year 1 but experienced regain; losses 5% were sustained at year 8 by non-Hispanic white participants and minority women (but not men). Session attendance was high ( 86%) in year 1 and exceeded protocol-specified minimum levels into year 8. Individual session attendance had stronger associations with weight loss among Hispanic and African American participants than non-Hispanic white participants at 4 years and 8 years. Daily self-weighing uptake was considerable in all subgroups and was a prominent factor associated with year 1 weight loss among African American men and women. Greater meal replacement use was strongly associated with poorer 1-year weight losses among African American women.